CN100560201C - Preparation technology's method of steroid 6 precedence methyl stereoselectivity hydrogenation catalyst - Google Patents
Preparation technology's method of steroid 6 precedence methyl stereoselectivity hydrogenation catalyst Download PDFInfo
- Publication number
- CN100560201C CN100560201C CNB2006101301270A CN200610130127A CN100560201C CN 100560201 C CN100560201 C CN 100560201C CN B2006101301270 A CNB2006101301270 A CN B2006101301270A CN 200610130127 A CN200610130127 A CN 200610130127A CN 100560201 C CN100560201 C CN 100560201C
- Authority
- CN
- China
- Prior art keywords
- value
- stirring
- preparation technology
- alkali lye
- active carbon
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Catalysts (AREA)
- Steroid Compounds (AREA)
Abstract
A kind of steroid 6 precedence methyl stereoselectivity is hydrogenated to preparation technology's method of the catalysts of 6 Alpha-Methyls; active carbon and deionized water and stirring is even; add hydrogen peroxide, sulfuric acid; regulate the pH value of heterogeneous mixed liquor greater than 7 with alkali lye after stirring; with alkali lye keep under this pH value 0～100 ℃ drip the chloride acid solution and reductant solution of group VIII metal down after; under this pH value and nitrogen protection, stir, filter, get catalyst.Perhaps that active carbon and deionized water and stirring is even; add hydrogen peroxide, sulfuric acid; after stirring; filter active carbon; again with active carbon and deionized water and stirring evenly the back regulate heterogeneous mixed liquor with alkali lye pH value greater than 7, with alkali lye keep under this pH value 0～100 ℃ descend the chloride acid solution and reductant solution of dropping group VIII metal after, under this pH value and nitrogen protection, stir; filter, get catalyst.This technology can make noble metal be adsorbed on the surface of absorbent charcoal carrier with smaller particles, and Zhi Bei catalyst is hydrogenated in the process of 6 Alpha-Methyls in the methine stereoselectivity to the steroid 6 position like this, has improved activity and selectivity.
Description
Technical field:
The present invention relates to preparation technology's method of corticoid pharmaceutical intermediate catalysts.
Background technology:
At normal temperatures and pressures carbon-carbon double bond hydrogenation reaction is often utilized the group VIII metallic catalyst in the organic synthesis, is adsorbed on as palladium, ruthenium, rhodium, platinum etc. and produces catalytic action on the powdered carbon.In steroidal was synthetic, 6 methine can carry out stereoselectivity hydrogenation by utilizing the group VIII metallic catalyst to be adsorbed on to produce catalytic action on the powdered carbon, obtains 6 Alpha-Methyl things.Mention among the document DE 3427486 utilize the palladium charcoal at ethanol-cyclohexene with 6-methine-4,9 (11)-androstane diene-3,17-diketone catalytic hydrogenation is 6 Alpha-Methyls-4,9 (11)-androstane diene-3, the 17-diketone.Similarly, 6 Alpha-Methyls of methylprednisolone also can obtain by this method.
Metallic catalyst is usually by the metal of group VIII in the periodic table of elements, be deposited on the absorbent charcoal carrier and make, this catalyst is applied in many hydrogenation reactions, and common preparation method is immersed in carrier in the salting liquid that contains the group VIII metal, reduces it then for the metal phase.In the stereoselectivity hydrogenation, the purpose of improving catalyst mainly be to lift from catalyst three-dimensional selective power, and be not only the raising that improves the catalyst hydrogenation ability.
The activity that is adsorbed on the group VIII metallic catalyst on the carrier is relevant with many factors with selectivity, as the type of carrier, the consumption of metal, the granularity that the metallic that different preparation methods causes distributes in steroidal, the degree of depth, the uniformity.
The preparation method of relevant charcoal absorption group VIII metallic catalyst, have some reports both at home and abroad, as Yang Kunguo report (chemical research, 2001,2,51) 3%Pd/C method for preparing catalyst: in palladium chloride solution, add and have in the solution of active carbon, stir and add formaldehyde after 8 hours, fully mix the back and drip NaOH solution to pH=12.5-13.0,40 degree constant temperature stir reductase 12s and filter after 4 hours, distilled water is washed till no chlorion, and 120 ℃ of dryings 21 hours are standby; Introduced a kind of production technology among the US2857337, palladium salt is handled with water miscible metal hydroxides or alkali formula charcoal hydrochlorate, is reduced to Metal Palladium by reducing agent again, and reducing agent has formaldehyde, glucose, hydrazine, glycerine etc.People such as Keith introduce in US3138560, and tetrachloro-palladium acid sodium or palladium bichloride are added drop-wise on the charcoal carrier, and most of palladium is deposited as glossiness Metal Palladium film immediately, and the catalyst activity of this method preparation is lower.Theoretically, this is that palladium salt directly is reduced into the cause of Metal Palladium by existing functional group such as aldehyde radical or free electron on the activated carbon surface, thereby causes metal migration and grain growth, so the catalyst that adopts this mode to prepare, specific activity is relatively poor, and unstable.
The sort of mode no matter, all inevitably run into a problem, the direct reduction problem of palladium when promptly adsorbing, the functional group of activated carbon surface such as aldehyde radical or free electron etc., the palladium salt that can directly reduce is palladium metal, mentions the improvement preparation method of palladium carbon catalyst among the US3138560, by adding the mode of oxidant, as tert-butyl peroxide, persulfate, perchloric acid etc., preferred hydrogen peroxide.Can prevent that palladium from being reduced immediately by the aldehyde radical of activated carbon surface or free electron after adding oxidant like this, and problems such as metal migration and grain growth can not take place.But adopt the catalyst of this method preparation, be hydrogenated in the process of 6 Alpha-Methyls in the methine stereoselectivity to the steroid 6 position, selectivity is not high, has wherein produced 6 more Beta-methyl things.
Summary of the invention:
The present invention is directed to the problem that prior art exists, provide a kind of methine stereoselectivity to be hydrogenated to the higher group VIII metallic catalyst of 6 Alpha-Methyl process neutral body selectivity in the steroid 6 position.The present invention mainly is at improving Preparation of catalysts technology, by changing charging sequence and the pH value in the catalyst preparation process, make noble metal be adsorbed on the surface of absorbent charcoal carrier with smaller particles, Zhi Bei catalyst is hydrogenated in the process of 6 Alpha-Methyls in the methine stereoselectivity to the steroid 6 position like this, has improved activity and selectivity.
A kind of steroid 6 precedence methyl stereoselectivity is hydrogenated to preparation technology's method of the catalysts of 6 Alpha-Methyls; it is characterized in that: active carbon and deionized water and stirring is even; add hydrogen peroxide, sulfuric acid; after stirring; the pH value of regulating heterogeneous mixed liquor with alkali lye is greater than 7, with alkali lye keep under this pH value 0～100 ℃ drip the chloride acid solution and reductant solution of group VIII metal down after, under this pH value and nitrogen protection, stir; filter, get catalyst.
A kind of steroid 6 precedence methyl stereoselectivity is hydrogenated to preparation technology's method of the catalysts of 6 Alpha-Methyls; it is characterized in that: active carbon and deionized water and stirring is even; add hydrogen peroxide, sulfuric acid; after stirring; filter active carbon; again active carbon and deionized water and stirring are evenly regulated the pH value of heterogeneous mixed liquor greater than 7 with alkali lye in the back; with alkali lye keep under this pH value 0～100 ℃ drip the chloride acid solution and reductant solution of group VIII metal down after; under this pH value and nitrogen protection, stir; filter, get catalyst.
As described above, alkali lye is regulated the pH value of heterogeneous mixed liquor between 8-11, between the preferred 8.5-9.5.
As described above, the temperature that drips the chloride acid solution of group VIII metal is 50～70 ℃, and the temperature that drips reductant solution is 20～40 ℃.
As described above, alkali lye is the solution of alkali metal salt.
As described above, the group VIII metal is a kind of of palladium, ruthenium, rhodium, platinum etc.
As described above, reducing agent is one or more in formaldehyde, potassium borohydride, lithium aluminium hydride reduction, glucose, hydrazine, the glycerine, preferred formaldehyde.
As described above, the volume ratio of hydrogen peroxide and sulfuric acid is 1: 1～1: 3.
As described above, should feed nitrogen in the course of reaction always.
With 6-methine-4,9 (11)-androstane dienes-3,17-diketone catalytic hydrogenation is 6 Alpha-Methyls-4,9 (11)-androstane dienes-3, the 17-diketone is an example, method according to document DE 3427486 only changes catalyst, with the content of 6 Alpha-Methyls of last generation and 6 Beta-methyl things to recently verifying the effect of catalyst.
In order to realize purpose of the present invention, the invention provides following technical scheme:
Active carbon and deionized water and stirring is even; add hydrogen peroxide, sulfuric acid (volume ratio is 1: 1～1: 3); after stirring; filter active carbon; again with active carbon and evenly back pH value to 8～10 of regulating heterogeneous mixed liquor with NaOH solution of deionized water and stirring; keep under this pH value at 50～70 ℃ of chloride acid solutions that drip the group VIII metal with alkali lye; drip formalin at 20～40 ℃ again; under this pH value and nitrogen protection, stir insulation 15-17 hour then; filter, get catalyst.
Excellent beneficial effect of the present invention can experimental results show that by following.
Table: steroid 6 precedence methyl stereoselectivity hydrogenation catalyst of the present invention and existing effect are relatively
| Numbering | Reactant 1 inventory (g) | The preparation method of hydrogenation catalyst | Product 2 output (g) | Yield % | 6 Alpha-Methyl thing % | 6 Beta-methyl thing % |
| 1 | 10 | Add hydrogen peroxide | 10.5 | 105 | 70 | 26 |
| 2 | 10 | Add perchloric acid | 10.1 | 101 | 60 | 38 |
| 3 | 10 | Add hydrogen peroxide: sulfuric acid (1: 1) | 11.06 | 110.6 | 90 | 9 |
| 4 | 10 | Add hydrogen peroxide: sulfuric acid (1: 2) | 11.08 | 110.8 | 91 | 7 |
| 5 | 10 | Add hydrogen peroxide: sulfuric acid (1: 3) | 11.07 | 110.7 | 92 | 6 |
Annotate: yield %=product 2 output/reactant 1 inventory * 100%
6 Alpha-Methyl thing %: the liquid content of 6 Alpha-Methyl things in the hydrogenation reaction product
6 Beta-methyl thing %: the liquid content of 6 Beta-methyl things in the hydrogenation reaction product
Above reactant 1 sample and product 2 samples can be found out the adding hydrogen peroxide from spectrogram through liquid chromatographic detection: the content of the made catalyst reaction gained 6 Alpha-Methyl things of sulfuric acid (volume ratio is 1: 1～1: 3) is obviously more than the content that adds hydrogen peroxide or the made catalyst reaction gained 6 Alpha-Methyl things of perchloric acid (prior art).
As can be seen from the above table, add hydrogen peroxide: product 2 yields and the content of the catalyst reaction gained that sulfuric acid (volume ratio is 1: 1～1: 3) is prepared all are significantly improved, and add hydrogen peroxide: the yield of the product of the catalyst reaction gained that sulfuric acid (volume ratio is 1: 1～1: 3) is prepared and the increase rate of content are basic identical.
This shows, excellent beneficial effect of the present invention is: by changing charging sequence and the pH value in the catalyst preparation process, readjusted reaction medium, and to reacting again after the preliminary treatment of active carbon process, make noble metal be adsorbed on the surface of absorbent charcoal carrier with smaller particles, Zhi Bei catalyst is hydrogenated in the process of 6 Alpha-Methyls in the methine stereoselectivity to the steroid 6 position like this, has improved activity and selectivity.
The specific embodiment:
Embodiment 1:
10g active carbon and deionized water and stirring is even, add hydrogen peroxide 20ml and sulfuric acid 40ml, after stirring, regulate the pH=9 of heterogeneous mixed liquor, and keep dripping 0ml10%PdCl at 60 ℃ under this pH value with 40%NaOH solution
2/ HCL solution drips 20ml formalin at 30 ℃ again, stirs insulation 15 hours then under this pH value and nitrogen protection, filters, and gets catalyst 12.1g.
Embodiment 2:
10g active carbon and deionized water and stirring is even, add hydrogen peroxide 20ml and sulfuric acid 20ml, after stirring, filter active carbon, again active carbon and deionized water and stirring are evenly regulated the pH=8.5 of heterogeneous mixed liquor with 40%NaOH solution in the back, and keep dripping 0ml10%PdCl at 50 ℃ under this pH value
2/ HCL solution drips 20ml formalin at 20 ℃ again, stirs insulation 15 hours then under this pH value and nitrogen protection, filters, and gets catalyst 12.2g.
Embodiment 3:
10g active carbon and deionized water and stirring is even, add hydrogen peroxide 20ml and sulfuric acid 40ml, after stirring, filter active carbon, again active carbon and deionized water and stirring are evenly regulated the pH=9 of heterogeneous mixed liquor with 40%NaOH solution in the back, and keep dripping 10ml10%PdCl at 60 ℃ under this pH value
2/ HCL solution drips 20ml formalin at 30 ℃ again, stirs insulation 16 hours then under this pH value and nitrogen protection, filters, and gets catalyst 12.4g.
Embodiment 4:
10g active carbon and deionized water and stirring is even, add hydrogen peroxide 20ml and sulfuric acid 60ml, after stirring, filter active carbon, again active carbon and deionized water and stirring are evenly regulated the pH=9.5 of heterogeneous mixed liquor with 40%NaOH solution in the back, and keep dripping 10ml10%PdCl at 70 ℃ under this pH value
2/ HCL solution drips 20ml formalin at 40 ℃ again, stirs insulation 17 hours then under this pH value and nitrogen protection, filters, and gets catalyst 12.5g.
Claims (9)
1. a steroid 6 precedence methyl stereoselectivity is hydrogenated to preparation technology's method of the catalysts of 6 Alpha-Methyls; it is characterized in that: active carbon and deionized water and stirring is even; add hydrogen peroxide, sulfuric acid; after stirring; the pH value of regulating heterogeneous mixed liquor with alkali lye is greater than 7, with alkali lye keep under this pH value 0～100 ℃ drip the chloride acid solution and reductant solution of group VIII metal down after, under this pH value and nitrogen protection, stir; filter, get catalyst.
2. a steroid 6 precedence methyl stereoselectivity is hydrogenated to preparation technology's method of the catalysts of 6 Alpha-Methyls; it is characterized in that: active carbon and deionized water and stirring is even; add hydrogen peroxide, sulfuric acid; after stirring; filter active carbon; again active carbon and deionized water and stirring are evenly regulated the pH value of heterogeneous mixed liquor greater than 7 with alkali lye in the back; with alkali lye keep under this pH value 0～100 ℃ drip the chloride acid solution and reductant solution of group VIII metal down after; under this pH value and nitrogen protection, stir; filter, get catalyst.
3. preparation technology's method as claimed in claim 1 or 2 is characterized in that alkali lye regulates the pH value of heterogeneous mixed liquor between 8-11.
4. preparation technology's method as claimed in claim 1 or 2 is characterized in that alkali lye regulates the pH value of heterogeneous mixed liquor between 8.5-9.5.
5. preparation technology's method as claimed in claim 1 or 2, the temperature that it is characterized in that dripping the chloride acid solution of group VIII metal is 50～70 ℃, the temperature that drips reductant solution is 20～40 ℃.
6. preparation technology's method as claimed in claim 1 or 2 is characterized in that reducing agent is one or more in formaldehyde, potassium borohydride, lithium aluminium hydride reduction, glucose, hydrazine, the glycerine.
7. preparation technology's method as claimed in claim 1 or 2 is characterized in that reducing agent is a formaldehyde.
8. preparation technology's method as claimed in claim 1 or 2, the volume ratio that it is characterized in that hydrogen peroxide and sulfuric acid is 1: 1～1: 3.
9. preparation technology's method as claimed in claim 1 or 2 is characterized in that should feeding nitrogen in the course of reaction always.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2006101301270A CN100560201C (en) | 2006-12-13 | 2006-12-13 | Preparation technology's method of steroid 6 precedence methyl stereoselectivity hydrogenation catalyst |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2006101301270A CN100560201C (en) | 2006-12-13 | 2006-12-13 | Preparation technology's method of steroid 6 precedence methyl stereoselectivity hydrogenation catalyst |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN101199927A CN101199927A (en) | 2008-06-18 |
| CN100560201C true CN100560201C (en) | 2009-11-18 |
Family
ID=39515399
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNB2006101301270A Active CN100560201C (en) | 2006-12-13 | 2006-12-13 | Preparation technology's method of steroid 6 precedence methyl stereoselectivity hydrogenation catalyst |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN100560201C (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115337936A (en) * | 2022-10-18 | 2022-11-15 | 无锡威孚环保催化剂有限公司 | Preparation of PtCo/C catalyst and method for catalyzing selective hydrogenation of alpha, beta-unsaturated aldehyde by using PtCo/C catalyst |
-
2006
- 2006-12-13 CN CNB2006101301270A patent/CN100560201C/en active Active
Non-Patent Citations (2)
| Title |
|---|
| 6-次甲基甾体化合物氢化条件的研究. 张水泉等.中国医药工业杂志，第12期. 1984 |
| 6-次甲基甾体化合物氢化条件的研究. 张水泉等.中国医药工业杂志，第12期. 1984 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN101199927A (en) | 2008-06-18 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN1130265C (en) | Catalyst capable of using on carrier in organic compound conversion reaction | |
| CN101347737B (en) | Selective hydrogenation catalyst of aromatic aldehydes for refinement of terephthalic acid | |
| CN100551523C (en) | A kind of metal oxide supported Nobel-metal catalyst preparation method | |
| CN102274724B (en) | High-activity catalyst used in hydrogenation reaction of aromatic nitro-compound and preparation method thereof | |
| CN106946894A (en) | Application of the Pd radicel duplex metal catalyst in HBIW catalytic hydrogenolytic cleavages | |
| CN106378194A (en) | Transition metal copper loaded UiO-66-NH2 composite catalyst, preparation method and application thereof | |
| CN104971759A (en) | Preparation method of supported palladium-carbon catalyst | |
| CN103386301B (en) | A kind of preparation method of steroid compound catalyst for hydrogenation and application | |
| JP2021526458A (en) | Precious metal-supported catalysts, their manufacturing methods, and applications | |
| CN110508278B (en) | In-situ monatomic Pd/mesoporous alumina catalyst and preparation method and application thereof | |
| CN101549292A (en) | Catalyst for synthesizing cyclohexene by hydrogenation of benzene ring and preparing method thereof | |
| CN103191760A (en) | Acetylene-hydrochlorinated low-content gold compound catalyst | |
| CN101544538B (en) | Method for preparing isopentenol from 3-methyl-3-butenol | |
| CN113388853B (en) | Electrochemical catalysis method for highly selective hydrogenation of carbon-carbon triple bonds | |
| CN108187676A (en) | A kind of ester through hydrogenation synthesis of dibasic alcohol copper-based catalysts and its preparation method and application | |
| CN112481655A (en) | Preparation method and application of Pd-Ru-Cu alloy type icosahedral nano-catalyst | |
| CN111111724B (en) | Calcium carbonate modified carbon material loaded nano palladium alloy catalyst and preparation method and application thereof | |
| CN101632929A (en) | Hydrogen production catalyst with high-temperature methyl alcohol water vapour and preparation method thereof | |
| CN100560201C (en) | Preparation technology's method of steroid 6 precedence methyl stereoselectivity hydrogenation catalyst | |
| CN109134201A (en) | The heterogeneous catalytic hydrogenation defluorination processing method of efficient degradation fluorobenzene phenolic compound | |
| CN105195147A (en) | Dehydrogenation catalyst with copper nanoparticles loaded inside carbon nano tube and preparation method of dehydrogenation catalyst | |
| CN102580748B (en) | Amorphous alloy catalyst for hydrogenating dinitrotoluene and application of amorphous alloy catalyst | |
| Wu et al. | Controlled synthesis of supported nickel boride catalyst using electroless plating | |
| CN112473679B (en) | Nickel-phyllosilicate structure catalyst and preparation method thereof | |
| CN114622239B (en) | PdCu-Ni (OH) 2 Catalyst, preparation method and application thereof in electrocatalytic urea synthesis |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| CP02 | Change in the address of a patent holder |
Address after: 300161 No. 19, Xinye 9th Street, West District, Binhai New Area Development Zone, Tianjin Patentee after: TIANJIN TIANYAO PHARMACEUTICAL Co.,Ltd. Address before: Cheng linzhuan Hedong District of Tianjin City Road 300161 No. 91 Patentee before: TIANJIN TIANYAO PHARMACEUTICAL Co.,Ltd. |
|
| CP02 | Change in the address of a patent holder | ||
| DD01 | Delivery of document by public notice |
Addressee: Li Jian Document name: Notification of Eligibility for Procedures |
|
| DD01 | Delivery of document by public notice | ||
| CP01 | Change in the name or title of a patent holder |
Address after: 300161 No. 19, Xinye 9th Street, West District, Binhai New Area Development Zone, Tianjin Patentee after: Tianjin Pharmaceutical Co.,Ltd. Address before: 300161 No. 19, Xinye 9th Street, West District, Binhai New Area Development Zone, Tianjin Patentee before: TIANJIN TIANYAO PHARMACEUTICAL Co.,Ltd. |
|
| CP01 | Change in the name or title of a patent holder |